Literature summary for 1.14.11.1 extracted from

Rydzik, A.M.; Leung, I.K.; Kochan, G.T.; Loik, N.D.; Henry, L.; McDonough, M.A.; Claridge, T.D.; Schofield, C.J.
Comparison of the substrate selectivity and biochemical properties of human and bacterial gamma-butyrobetaine hydroxylase (2014), Org. Biomol. Chem., 12, 6354-6358 .

Search for more literature for 1.14.11.1

Activating Compound

Activating Compound	Comment	Organism	Structure
ascorbate	required	Homo sapiens

Application

Application	Comment	Organism
medicine	BBOX is a therapeutic target in humans, the BBOX inhibitor mildronate is used to decrease fatty acid oxidation in patients after myocardial infarction	Homo sapiens

Cloned(Commentary)

Cloned (Comment)	Organism
gene BBOX1, recombinant expression of His-tagged codon-optimized enzyme in Escherichia coli strain BL21(DE3)	Homo sapiens
recombinant expression of N-terminally His-tagged codon-optimized enzyme in Escherichia coli strain BL21(DE3)	Pseudomonas sp.

Crystallization (Commentary)

Crystallization (Comment)	Organism
crystal structure analysis, PDB ID 3O2G	Homo sapiens

Inhibitors

Inhibitors	Comment	Organism
(3R)-3-fluoro-4-(trimethylammonio)butanoate	-	Homo sapiens
3-carboxy-N-(fluoromethyl)-N,N-dimethylpropan-1-aminium	-	Homo sapiens
4-Trimethylammoniobutanoate	substrate inhibition	Homo sapiens
4-Trimethylammoniobutanoate	substrate inhibition at high concentrations	Pseudomonas sp.
mildronate	-	Homo sapiens
N-oxalylglycine	-	Homo sapiens
N-oxalylglycine	binding structure modeling	Pseudomonas sp.
Ni2+	binding structure modeling	Pseudomonas sp.

KM Value [mM]

KM Value [mM]	KM Value Maximum [mM]	Substrate	Comment	Organism
additional information	-	additional information	Michaelis-Menten kinetics	Homo sapiens
additional information	-	additional information	Michaelis-Menten kinetics	Pseudomonas sp.
0.0042	-	4-Trimethylammoniobutanoate	pH 7.5, temperature not specified in the publication	Homo sapiens
0.02	-	(3R)-3-fluoro-4-(trimethylammonio)butanoate	pH 7.5, temperature not specified in the publication	Homo sapiens
0.02	-	(2S)-3-carboxy-N-(fluoromethyl)-2-hydroxy-N,N-dimethylpropan-1-aminium	pH 7.5, temperature not specified in the publication	Homo sapiens
0.153	-	2-oxoglutarate	pH 7.5, temperature not specified in the publication	Homo sapiens
0.163	-	4-Trimethylammoniobutanoate	pH 7.5, temperature not specified in the publication, only the Michaelis-Menten range is fitted	Pseudomonas sp.
0.412	-	(2S)-3-carboxy-N-(fluoromethyl)-2-hydroxy-N,N-dimethylpropan-1-aminium	pH 7.5, temperature not specified in the publication	Pseudomonas sp.
0.532	-	2-oxoglutarate	pH 7.5, temperature not specified in the publication	Pseudomonas sp.
0.623	-	(3R)-3-fluoro-4-(trimethylammonio)butanoate	pH 7.5, temperature not specified in the publication	Pseudomonas sp.
2.474	-	4-Trimethylammoniobutanoate	pH 7.5, temperature not specified in the publication, the whole range is fitted	Pseudomonas sp.

Metals/Ions

Metals/Ions	Comment	Organism
Fe2+	nonheme Fe2+-dependent oxygenase, dependent on, required for catalysis	Homo sapiens
Fe2+	nonheme Fe2+-dependent oxygenase, dependent on, required for catalysis	Pseudomonas sp.
additional information	Ni2+ cannot substitute for Fe2+	Pseudomonas sp.

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.
4-trimethylammoniobutanoate + 2-oxoglutarate + O2	Homo sapiens	-	3-hydroxy-4-trimethylammoniobutanoate + succinate + CO2	-	?
4-trimethylammoniobutanoate + 2-oxoglutarate + O2	Pseudomonas sp.	-	3-hydroxy-4-trimethylammoniobutanoate + succinate + CO2	-	?
4-trimethylammoniobutanoate + 2-oxoglutarate + O2	Pseudomonas sp. AK-1	-	3-hydroxy-4-trimethylammoniobutanoate + succinate + CO2	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	O75936	-	-
Pseudomonas sp.	P80193	-	-
Pseudomonas sp. AK-1	P80193	-	-

Purification (Commentary)

Purification (Comment)	Organism
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography, gel filtration, and anion exchange chromatography	Homo sapiens
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography, gel filtration, and anion exchange chromatography, to over 90% purity	Pseudomonas sp.

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.
(3R)-3-fluoro-4-(trimethylammonio)butanoate + 2-oxoglutarate + O2	-	Homo sapiens	3-carboxy-N,N,N-trimethyl-2-oxopropan-1-aminium + succinate + formylfluoride	-	?
(3R)-3-fluoro-4-(trimethylammonio)butanoate + 2-oxoglutarate + O2	-	Pseudomonas sp.	3-carboxy-N,N,N-trimethyl-2-oxopropan-1-aminium + succinate + formylfluoride	-	?
(3R)-3-fluoro-4-(trimethylammonio)butanoate + 2-oxoglutarate + O2	-	Pseudomonas sp. AK-1	3-carboxy-N,N,N-trimethyl-2-oxopropan-1-aminium + succinate + formylfluoride	-	?
(R)-2-amino-3-carboxy-N,N,N-trimethylpropan-1-aminium + 2-oxoglutarate + O2	-	Pseudomonas sp.	N-[(3R)-3-amino-3-carboxy-2-hydroxypropyl]-N,N-dimethylmethanaminium + succinate + CO2	-	?
(R)-2-amino-3-carboxy-N,N,N-trimethylpropan-1-aminium + 2-oxoglutarate + O2	-	Pseudomonas sp. AK-1	N-[(3R)-3-amino-3-carboxy-2-hydroxypropyl]-N,N-dimethylmethanaminium + succinate + CO2	-	?
(S)-2-amino-3-carboxy-N,N,N-trimethylpropan-1-aminium + 2-oxoglutarate + O2	-	Pseudomonas sp.	N-[(3S)-3-amino-3-carboxy-2-hydroxypropyl]-N,N-dimethylmethanaminium + succinate + CO2	-	?
(S)-2-amino-3-carboxy-N,N,N-trimethylpropan-1-aminium + 2-oxoglutarate + O2	-	Pseudomonas sp. AK-1	N-[(3S)-3-amino-3-carboxy-2-hydroxypropyl]-N,N-dimethylmethanaminium + succinate + CO2	-	?
(S)-3-carboxy-2-hydroxy-N,N,N-trimethylpropan-1-aminium + 2-oxoglutarate + O2	-	Pseudomonas sp.	(3S)-3-carboxy-2,3-dihydroxy-N,N,N-trimethylpropan-1-aminium + succinate + CO2	-	?
2-carboxy-N,N,N-trimethylethan-1-aminium + 2-oxoglutarate + O2	-	Homo sapiens	4-carboxy-3-hydroxy-N,N,N-trimethylbutan-1-aminium + succinate + CO2	-	?
2-carboxy-N,N,N-trimethylethan-1-aminium + 2-oxoglutarate + O2	-	Pseudomonas sp.	4-carboxy-3-hydroxy-N,N,N-trimethylbutan-1-aminium + succinate + CO2	-	?
3-carboxy-N-(fluoromethyl)-N,N-dimethylpropan-1-aminium + 2-oxoglutarate + O2	-	Homo sapiens	(2S)-3-carboxy-N-(fluoromethyl)-2-hydroxy-N,N-dimethylpropan-1-aminium + succinate + CO2	-	?
3-carboxy-N-(fluoromethyl)-N,N-dimethylpropan-1-aminium + 2-oxoglutarate + O2	-	Pseudomonas sp.	(2S)-3-carboxy-N-(fluoromethyl)-2-hydroxy-N,N-dimethylpropan-1-aminium + succinate + CO2	-	?
4-trimethylammoniobutanoate + 2-oxoglutarate + O2	-	Homo sapiens	3-hydroxy-4-trimethylammoniobutanoate + succinate + CO2	-	?
4-trimethylammoniobutanoate + 2-oxoglutarate + O2	-	Pseudomonas sp.	3-hydroxy-4-trimethylammoniobutanoate + succinate + CO2	-	?
4-trimethylammoniobutanoate + 2-oxoglutarate + O2	-	Pseudomonas sp. AK-1	3-hydroxy-4-trimethylammoniobutanoate + succinate + CO2	-	?
4-trimethylammoniopropanoate + 2-oxoglutarate + O2	-	Homo sapiens	2-carboxy-2-hydroxy-N,N,N-trimethylethan-1-aminium + succinate + CO2	-	?
D-carnitine + 2-oxoglutarate + O2	-	Homo sapiens	3-carboxy-N,N,N-trimethyl-2-oxopropan-1-aminium + succinate + CO2	-	?
D-carnitine + 2-oxoglutarate + O2	-	Pseudomonas sp.	3-carboxy-N,N,N-trimethyl-2-oxopropan-1-aminium + succinate + CO2	-	?
L-carnitine + 2-oxoglutarate + O2	-	Homo sapiens	3-carboxy-N,N,N-trimethyl-2-oxopropan-1-aminium + succinate + CO2	-	?
additional information	no activity with trimethyllysine, acetylcholine, phosphocholine, thioacetylcholine, carbachol, and gamma-butyrobetaine analogues carboxy-N,N,N-trimethylmethanaminium, 5-carboxy-N,N,N-trimethylpentan-1-aminium, N,N,N-trimethyl-4-oxopentan-1-aminium, and 4-methoxy-N,N,N-trimethyl-4-oxobutan-1-aminium, substrate specificity, overview	Homo sapiens	?	-	?
additional information	no activity with trimethyllysine, acetylcholine, phosphocholine, thioacetylcholine, carbachol, and gamma-butyrobetaine analogues carboxy-N,N,N-trimethylmethanaminium, 5-carboxy-N,N,N-trimethylpentan-1-aminium, N,N,N-trimethyl-4-oxopentan-1-aminium, and 4-methoxy-N,N,N-trimethyl-4-oxobutan-1-aminium, substrate specificity, overview	Pseudomonas sp.	?	-	?
additional information	no activity with trimethyllysine, acetylcholine, phosphocholine, thioacetylcholine, carbachol, and gamma-butyrobetaine analogues carboxy-N,N,N-trimethylmethanaminium, 5-carboxy-N,N,N-trimethylpentan-1-aminium, N,N,N-trimethyl-4-oxopentan-1-aminium, and 4-methoxy-N,N,N-trimethyl-4-oxobutan-1-aminium, substrate specificity, overview	Pseudomonas sp. AK-1	?	-	?

Subunits

Subunits	Comment	Organism
More	homology structure modelling	Homo sapiens
More	homology structure modelling	Pseudomonas sp.

Synonyms

Synonyms	Comment	Organism
BBOX	-	Homo sapiens
BBOX	-	Pseudomonas sp.
gamma-butyrobetaine hydroxylase	-	Homo sapiens
gamma-butyrobetaine hydroxylase	-	Pseudomonas sp.
hBBOX	-	Homo sapiens
psBBOX	-	Pseudomonas sp.

Turnover Number [1/s]

Turnover Number Minimum [1/s]	Turnover Number Maximum [1/s]	Substrate	Comment	Organism
0.059	-	(3R)-3-fluoro-4-(trimethylammonio)butanoate	pH 7.5, temperature not specified in the publication	Pseudomonas sp.
0.14	-	(3R)-3-fluoro-4-(trimethylammonio)butanoate	pH 7.5, temperature not specified in the publication	Homo sapiens
0.3	-	(2S)-3-carboxy-N-(fluoromethyl)-2-hydroxy-N,N-dimethylpropan-1-aminium	pH 7.5, temperature not specified in the publication	Homo sapiens
0.83	-	4-Trimethylammoniobutanoate	pH 7.5, temperature not specified in the publication	Homo sapiens
1.6	-	2-oxoglutarate	pH 7.5, temperature not specified in the publication	Homo sapiens
3.5	-	2-oxoglutarate	pH 7.5, temperature not specified in the publication	Pseudomonas sp.
5	-	(2S)-3-carboxy-N-(fluoromethyl)-2-hydroxy-N,N-dimethylpropan-1-aminium	pH 7.5, temperature not specified in the publication	Pseudomonas sp.
21.3	-	4-Trimethylammoniobutanoate	pH 7.5, temperature not specified in the publication	Pseudomonas sp.

pH Optimum

pH Optimum Minimum	pH Optimum Maximum	Comment	Organism
7.5	-	assay at	Homo sapiens
7.5	-	assay at	Pseudomonas sp.

Ki Value [mM]

Ki Value [mM]	Ki Value maximum [mM]	Inhibitor	Comment	Organism
0.024	-	4-Trimethylammoniobutanoate	pH 7.5, temperature not specified in the publication	Homo sapiens
0.125	-	4-Trimethylammoniobutanoate	pH 7.5, temperature not specified in the publication	Pseudomonas sp.
0.136	-	(3R)-3-fluoro-4-(trimethylammonio)butanoate	pH 7.5, temperature not specified in the publication	Homo sapiens
0.226	-	3-carboxy-N-(fluoromethyl)-N,N-dimethylpropan-1-aminium	pH 7.5, temperature not specified in the publication	Homo sapiens

General Information

General Information	Comment	Organism
evolution	comparison of properties, substrate specificities, and structures of the human enzyme (PDB ID 3O2G) and the enzyme from Pseudomonas sp. AK1, detailed overview	Homo sapiens
evolution	comparison of properties, substrate specificities, and structures of the human enzyme (PDB ID 3O2G) and the enzyme from Pseudomonas sp. AK1, detailed overview	Pseudomonas sp.
metabolism	gamma-butyrobetaine hydroxylase (BBOX) catalyses the final step in the biosynthesis of carnitine i.e. the stereoselective hydroxylation of gamma-butyrobetaine (GBB)	Homo sapiens
metabolism	gamma-butyrobetaine hydroxylase (BBOX) catalyses the final step in the biosynthesis of carnitine i.e. the stereoselective hydroxylation of gamma-butyrobetaine (GBB)	Pseudomonas sp.
additional information	homology structure modeling with bound Ni2+ and N-oxalglycine, modeled based on human BBOX structure, DB ID 2O2G	Pseudomonas sp.